Misialek: I am interested in learning more about the patients behind my slides. I invited Linnea to the lab, where I showed her different lung cancers under the microscope, including her specific cancer type.
Olson: After I was diagnosed with non-small cell lung cancer in April of 2005, I wrote a letter of thanks to the pathologist. I was so very grateful that I now had a credible explanation for the cough, shortness of breath, and general malaise that my general practitioner had misattributed to adult onset asthma. As an information-based individual, even though a diagnosis of lung cancer was devastating, knowing the actual cause of my symptoms was a huge relief.
Misialek: I’ve been a pathologist for 17 years. Most of my work is with microscope slides that bear small smears of stained tissue. I scrutinize them to find an answer for a patient’s symptoms, to make a diagnosis, or to assess the response to treatment. The first time a patient’s cells are illuminated under the microscope represents to me a new challenge that must be answered.
Although I rarely have the opportunity to interact directly with patients, I am often the physician that first makes the diagnosis, an important first step in caring for a patient. But my involvement doesn’t end there. Additional information is often needed to tailor treatment or gauge effectiveness. Pathology is essential not just for diagnosis but also in health and the prevention of disease. The role of the pathologist has taken on greater meaning in this era of precision medicine.
When I visited Michael in the lab, it was the most extensive view I’ve ever had of lung cancer slides under the microscope. I had never held a lung before, and seeing what a tumor actually looked like was mind-blowing. It is so different than how it appears on CT or MRI scans. Seeing one in real life gave me a greater appreciation for how a tumor invades healthy tissue.
I was already working on some pieces that were more autobiographical, so it was cool to see more intimately what is going on inside the body. Tissue freshly removed from the body (like the lung Michael showed me) is so very different than what we usually see in photos or how it is represented in models or drawings. It is so obviously alive — like the difference between a living tree and a piece of wood. The microscope slides were another window into the complex processes going on inside each of us that we are often oblivious to. I find it all fascinating and inspiring and it has informed both my painting and some multimedia pieces I am working on.
Misialek: Pathology is both an art and a science. There is art in making a diagnosis. On another level, there is art to the colors and patterns of cells under the microscope, just like Linnea’s pigments on canvas. Lung cancer appears as masses of foreign cells, recognizable at low magnification. The delicate sponge-like lattice of normal lung tissue is violated by infiltrating cancer cells, breaking up the harmonious pattern, wreaking havoc on the body.
Courtesy Linnea Olson – Scans of Linnea’s tumor before crizotinib (left) and after.
Olson: My cancer was classified as bronchial alveolar carcinoma mucinous — now referred to as invasive mucinous adenocarcinoma. It came as a surprise, because I was young at the time (45) and wasn’t a smoker.
Misialek: Mucinous adenocarcinoma cells spill the mucus they accumulate. Under the microscope, they look like oil tankers with breached hulls.
Olson: My tumor was relatively large (5 centimeters) but all of the nearby lymph nodes that were removed were clear of cancer. A sample of my tissue was submitted for genetic screening.
Misialek: Perhaps no greater example of the power of precision medicine is the way that it has transformed our approach to lung cancer. In 1987, scientists found that the epidermal growth factor receptor (EGFR), which sits on the surface of lung cancer cells, could be a target for treatment. This receptor acts as an important regulator of cellular functions, ultimately controlling cell survival, tumor growth, invasion, and spread. In 2003, the FDA approved gefitinib (Iressa), the first drug that homes in on EGFR, beginning an era of targeted therapy. Others have been approved since then. Pathologists at Massachusetts General Hospital studied Linnea’s tumor, unraveling and reading its unique genetic code, searching for an Achilles heel. Unfortunately, Linnea’s tumor did not carry an EGFR mutation.
Olson: My initial treatment was a lobectomy — an operation to remove the lower lobe of my left lung. That was followed by four rounds of chemotherapy. I had hoped this would cure my cancer, but it returned almost immediately. With no further viable treatments, we began a period of watching and waiting. Each subsequent scan of my lungs showed additional cancerous nodules. By the summer of 2008, I had more than 33 tumors in my lungs, and a biopsy confirmed that it was spreading beyond the lung. Given three to five months to live, I tried a last ditch therapy with a drug called erlotinib (Tarceva). Not only did my cancer get worse, but I experienced all of the side effects. However, my oncologist had an encouraging bit of news. Genetic screening of tissue removed at my latest biopsy had come back positive for what’s known as an EML4-ALK translocation. This mutation supports the unregulated growth of non-small cell lung cancer cells. That mutation let me enroll in a clinical trial and, on Oct. 1, 2008, I became the fourth person in the world with non-small cell lung cancer to take an experimental drug called crizotinib (now marketed as Xalkori).
